Medical interventions have arisen from this basic science work, beginning with vaccines for infectious diseases, to the more recent development of monoclonal antibodies used to treat a variety of diseases. The total impact of immunological interventions, vaccinations in particular, on human health has been great, especially when considering molecular-based health interventions. Despite these medical successes and a good understanding of basic mechanisms of immunity, it appears as though we have only scratched the surface.

As technological breakthroughs have enabled ever more sophisticated research tools, additional layers of complexity have been revealed. For example, new immune cell subtypes (i.e. cells with differing Inhibitors,research,lifescience,medical functionality at a given condition) have been discovered such that the estimates for the total number of distinct cell subtypes now number in the hundreds. As in Inhibitors,research,lifescience,medical other large complex systems, cooperativity and cross-talk abound in the immune system, and these likely play a key role, as protective immunity is ultimately an emergent phenomenon whose functionality is greater than the sum of its parts. A view with this richness in mind would suggest that our understanding of how the immune system functions as a whole is very limited. At the clinical level, despite its AP24534 importance for general health, many aspects of the immune system are mostly ignored, and little is known about the variation Inhibitors,research,lifescience,medical in immune system components

and their functions. The standard “complete blood count” (CBC), one of the most commonly prescribed tests by physicians, is indicative of a recent infection or extreme disease cases such as drastic reduction in cell counts (Figure 1A). First used clinically in 1957, the test enumerates the five major leukocyte Inhibitors,research,lifescience,medical classes in blood based on cell shape and size (later automated versions of this assay replaced shape with electrical impedance). Yet enumeration of the many immune

cell subtypes, discovered since and identified through the specific expression of protein markers, is not achievable through a CBC test. Inhibitors,research,lifescience,medical In specific cases, flow cytometry is Tolmetin used clinically for enumerating additional cell subsets. Yet such profiling is performed only in specific disease cases to confirm a disease association (e.g. TH17 cell dysfunction in autoimmunity), or to monitor immune reconstitution (e.g. B, CD4+/CD8+ T cells ratio in bone-marrow transplant) rather than prospectively for prevention or early detection. Moreover, such clinical immunology testing assays are performed at a cell subset resolution far below the complexity known to exist in the immune system, yielding partial results inferred over heterogeneous cell types. With such scant collected data, the clinical implication of fluctuations of immune cell subsets among either healthy or diseased individuals is not known, nor is the relationship between subsets quantified or normal ranges tailored to an individual’s background.